Tropheryma whipplei (TW) is Gram-positive bacillus, a kind of opportunistic pathogen, which can cause Whipple's disease. Caused by TW infection, TW pneumonia is relatively rare and lacks specific clinical symptoms. It is difficult to be detected through traditional pathogen culture methods and is prone to be misdiagnosed in clinical practice. This paper reports a case of acquired immunodeficiency syndrome (AIDS) patient with severe pneumonia caused by TW and Pneumocystis jiroveci, confirmed by metagenomic next-generation sequencing (mNGS) and successfully treated. Based on mNGS results, antimicrobial and anti-inflammatory treatments were continuously adjusted, till the patient improved and were ultimately discharged.